Tuesday, 29 November, 2011

When inflexibility is counterproductive

Mechanism of UV-induced DNA Dewar lesion revealed

Excessive exposure to ultraviolet (UV) radiation of sunlight can result in skin damage and may even induce skin cancers. Irradiation with UV light causes mutations in the DNA, which can interfere with or even inhibit the read-out of genetic information and hence affect the cell function. The Dewar lesion is one of the major UV-induced reaction products, which can itself generate mutations. Understanding the mechanism that leads to the formation of the Dewar lesion is therefore of great interest. LMU Munich researchers have now shown that the DNA backbone (the double-stranded scaffold which bears the subunits that encode the genetic information) plays a decisive role in the process. The Dewar lesion can be generated only if the backbone of the DNA is intact. If the DNA strand itself is broken, and therefore more flexible, the Dewar reaction will not take place. The process reveals a surprisingly paradoxical facet of the DNA structure. On the one hand, an unbroken backbone is a prerequisite for DNA function and for cell survival; on the other, the intact backbone favors the formation of Dewar lesions upon exposure to UV, and so facilitates UV-induced mutagenesis. (Angewandte Chemie, 23 November 2011)